DESC:FIELD
The present disclosure relates to a process for the preparation of 4-ethanesulfonyl-2-nitroaniline.
BACKGROUND
4-Ethanesulfonyl-2-nitroaniline is used as an intermediate for preparing dyes and pH indicators. It is also used in the manufacturing of UV stabilizers and optical brighteners.
Conventionally, 4-ethanesulfonyl-2-nitroaniline is prepared by amination of 2-nitro-4-ethylsulfonechlorobenzene, wherein chloro substituent is displaced by the amino group using aqueous ammonia at 150°C. The reaction is carried out under harsh conditions and needs special equipment, thereby making the process un-economical.
4-Ethanesulfonyl-2-nitroaniline can also be prepared by alkylation of the sulfonyl group of 4-amino-3-nitro-benzenesulphonic acid. However, it is difficult to alkylate the sulfonyl group in the presence of the unprotected amine group, thereby necessitating protection of the amine group. This process is associated with drawbacks such as multiple steps, and obtaining a product with low yield and low purity.
There is, therefore, felt a need for a simple and an economical process for the preparation of 4-ethanesulfonyl-2-nitroaniline.
OBJECTS
Some of the objects of the present disclosure, which at least one embodiment herein satisfies, are as follows:
An object of the present disclosure is to ameliorate one or more problems of the prior art or to at least provide a useful alternative.
Another object of the present disclosure is to provide a simple process for the preparation of 4-ethanesulfonyl-2-nitroaniline.
Yet another object of the present disclosure is to provide an economical process for the preparation of 4-ethanesulfonyl-2-nitroaniline.
Other objects and advantages of the present disclosure will be more apparent from the following description, which is not intended to limit the scope of the present disclosure.
SUMMARY
The present disclosure is related to a process for the preparation of 4-ethanesulfonyl-2-nitroaniline.
The process of preparing 4-ethanesulfonyl-2-nitroaniline from 4-thiocyano-2-nitroaniline involves the alkylation of 4-thiocyano-2-nitroaniline to obtain 2-nitro-4-(ethylthio)aniline, followed by the oxidation of 2-nitro-4-(ethylthio)aniline to obtain 4-ethanesulfonyl-2-nitroaniline.
Alkylation of 4-thiocyano-2-nitroaniline is carried out with an alkylating agent in the presence of at least one alkali, at least one reducing agent, at least one phase transfer catalyst, and at least one first fluid medium to obtain 2-nitro-4-(ethylthio)aniline.
The alkali, the alkylating agent, the reducing agent, and the phase transfer catalyst are added to a mixture of 4-thiocyano-2-nitroaniline and the first fluid medium in one or more parts while maintaining the temperature of the mixture in the range of 20°C to 60°C. The first fluid medium is water. The alkali is selected from the group consisting of sodium hydroxide, potassium hydroxide, sodium carbonate, and potassium carbonate, and the mole ratio of 4-thiocyano-2-nitroaniline and the alkali is in the range of 1:4 to 1:8. The alkylating agent is selected from the group consisting of di-ethyl sulfate and ethyl bromide, and the mole ratio of 4-thiocyano-2-nitroaniline and the alkylating agent is in the range of 1:1 to 1:5. The reducing agent is sodium hydrosulfide, and the mole ratio of 4-thiocyano-2-nitroaniline and the reducing agent is in the range of 1:0.5 to 1:1. The phase transfer catalyst is selected from the group consisting of tetra-n-butylammonium bromide, methyltrioctylammonium chloride, hexadecyltributylphosphonium bromide, and crown ethers, and the mole ratio of 4-thiocyano-2-nitroaniline and the phase transfer catalyst is in the range of 1:0.005 to 1:0.05.
Further, oxidation of 2-nitro-4-(ethylthio)aniline is carried out with an oxidizing agent in the presence of at least one metal catalyst, and at least one acid to obtain 4-ethanesulfonyl-2-nitroaniline.
The oxidizing agent is selected from the group consisting of hydrogen peroxide, and m-chloroperbenzoic acid, and the mole ratio of 4-thiocyano-2-nitroaniline and the oxidizing agent is in the range of 1:2 to 1:3. The metal catalyst used is sodium tungstate, and the mole ratio of 4-thiocyano-2-nitroaniline and the metal catalyst is in the range of 1:0.005 to 1:0.05.
The acid used is acetic acid, and the mole ratio of 4-thiocyano-2-nitroaniline and the acid is in the range of 1:1 to 1:3.
The process of preparing 4-ethanesulfonyl-2-nitroaniline is described in detail as follows:
A reactor is charged with 4-thiocyano-2-nitroaniline and the first fluid medium to obtain a mixture. The alkali, the alkylating agent, the reducing agent, and the phase transfer catalyst are added to the mixture of 4-thiocyano-2-nitroaniline and the first fluid medium in one or more parts to obtain a first reaction mixture. The total amount of the phase transfer catalyst is added in one part. The alkali is added in 4 to 10 parts, wherein amount of each part of the alkali is in the range of 5% to 50% of the total amount of the alkali. The alkylating agent is added in 2 to 8 parts, wherein amount of each part of the alkylating agent is in the range of 10% to 50% of the total amount of the alkylating agent; and the reducing agent is added in 2 to 6 parts, wherein amount of each part of the reducing agent is in the range of 15% to 75% of the total amount of the reducing agent.
The first reaction mixture is stirred at a temperature in the range 20°C to 60°C for a time period in the range of 1 hour to 10 hours. Stirring is stopped and the resultant mixture is allowed to stand to obtain a bi-phasic mixture comprising an aqueous phase and an organic phase containing 2-nitro-4-(ethylthio)aniline. The organic phase and the aqueous phase are separated from the bi-phasic mixture. The separated aqueous phase is extracted with at least one second fluid medium, wherein the second fluid medium is at least one selected from the group consisting of chlorobenzene, toluene, and benzene. The extract/s are mixed with the separated organic phase to obtain a second reaction mixture comprising 2-nitro-4-(ethylthio)aniline.
The acid and the metal catalyst are added to the second reaction mixture and stirred at a temperature in the range of 30°C to 100°C for a time period in the range of 1 hour to 10 hours. The oxidizing agent is added over a time period in the range of 2 hours to 5 hours while maintaining the temperature in the range of 30°C to 100°C for a time period in the range of 1 hour to 10 hours to obtain a product mixture.
The product mixture is cooled to a temperature in the range of 10°C to 25°C and water is added to it to obtain a suspension comprising a solid fraction containing 4-ethanesulfonyl-2-nitroaniline and a liquid fraction. The solid fraction containing 4-ethanesulfonyl-2-nitroaniline is separated from the suspension to obtain a residue. The residue is washed with a third fluid medium and dried to obtain 4-ethanesulfonyl-2-nitroaniline. The third fluid medium is at least one selected from a group of fluids consisting of chlorobenzene, toluene, benzene, DCM, and ethyl acetate.
DETAILED DESCRIPTION
4-Ethanesulfonyl-2-nitroaniline is used as an intermediate in the preparation of synthetic dyes. It is also used as an intermediate for the preparation of various pH indicators, in the manufacturing of UV stabilizers and optical brighteners. The present disclosure envisages a simple and an economical process for the preparation of 4-ethanesulfonyl-2-nitroaniline.
The present disclosure provides a process for the preparation of 4-ethanesulfonyl-2-nitroaniline (I):

In accordance with the present disclosure, there is provided a process for preparing 4-ethanesulfonyl-2-nitroaniline (I). The process of the present disclosure involves following steps:
Alkylation of 4-thiocyano-2-nitroaniline (II) with at least one alkylating agent in the presence of at least one alkali, at least one reducing agent, at least one phase transfer catalyst and at least one first fluid medium to obtain 2-nitro-4-(ethylthio)aniline (III); and oxidation of 2-nitro-4-(ethylthio)aniline (III) by at least one oxidizing agent in the presence of at least one acid, and at least one metal catalyst, to obtain 4-ethanesulfonyl-2-nitroaniline (I).
The process for the preparation of 4-ethanesulfonyl-2-nitroaniline (I), in accordance with the present disclosure, is represented as Scheme I:

The preparation of 4-ethanesulfonyl-2-nitroaniline, in accordance with the present disclosure is described herein below:
A reactor is charged with compound of Formula II and a first fluid medium under continuous stirring to obtain a mixture. The alkali, the alkylating agent, the phase transfer catalyst, and the reducing agent are added in one or more parts to the mixture to obtain a first reaction mixture. The alkali, the alkylating agent, the reducing agent, and the phase transfer catalyst are added to the mixture of 4-thiocyano-2-nitroaniline and the first fluid medium in one or more parts while maintaining the temperature of the mixture in the range of 20°C to 60°C.
The first reaction mixture is stirred at a temperature in the range of 20°C to 60°C for a time period in the range of 1 hour to 10 hours. Stirring is stopped and the resultant mixture is allowed to stand to obtain a bi-phasic mixture comprising an aqueous phase, and an organic phase containing compound of Formula III.
The organic phase containing compound of Formula III and the aqueous phase are separated from the bi-phasic mixture. The separated aqueous phase is extracted with at least one second fluid medium. The extract/s are mixed with the organic phase to obtain a second reaction mixture comprising compound of Formula III.
The acid and the metal catalyst are added to the second reaction mixture followed by stirring at a temperature in the range of 30°C to 100°C for a time period in the range of 1 hour to 10 hours. The oxidizing agent is added over a time period in the range of 2 hours to 5 hours while maintaining the temperature in the range of 30°C to 100°C for a time period in the range of 1 hour to 10 hours to obtain a product mixture.
The product mixture is cooled to a temperature in the range of 10°C to 25°C and water is added to the cooled product mixture to obtain a suspension comprising a solid fraction containing compound of Formula I and a liquid fraction. The solid fraction containing compound of Formula I is separated by filtration from the suspension to obtain a residue.
The residue so obtained is washed with a third fluid medium and dried to obtain the compound of Formula I.
In accordance with the embodiments of the present disclosure, the addition of the alkali, the alkylating agent, the phase transfer catalyst, and the reducing agent to the mixture of compound of Formula II and the first fluid medium is carried out in one or more parts.
In accordance with the embodiments of the present disclosure, the total amount of the phase transfer catalyst is added in one part.
In accordance with the embodiments of the present disclosure, the alkali is added in 4 to 10 parts. The amount of each part of the alkali is in the range of 5% to 50% of the total amount of the alkali.
In accordance with the embodiments of the present disclosure, the alkylating agent is added in 2 to 8 parts. The amount of each part of the alkylating agent is in the range of 10% to 50% of the total amount of the alkylating agent.
In accordance with the embodiments of the present disclosure, the reducing agent is added in 2 to 6 parts. The amount of each part of the reducing agent is 15% to 75% of the total amount of the reducing agent.
In accordance with one embodiment of the present disclosure, the addition of the alkali, the alkylating agent, the phase transfer catalyst, and the reducing agent to the mixture of compound of Formula II and the first fluid medium is carried out in the following manner.
Initially, total amount of the phase transfer catalyst, a first part of the alkali, and a first part of the alkylating agent are added to the mixture of compound of Formula II and the first fluid medium. The first part of the alkali, and the first part of the alkylating agent are in the range of 30% to 40% of the total amount of the alkali and the alkylating agent respectively.
Further, a second part of the alkali, a second part of the alkylating agent and a first part of the reducing agent are added to the mixture of compound of Formula II and the first fluid medium. The second part of the alkali, and the second part of the alkylating agent is in the range of 5% to 15% of the total amount the alkali and the alkylating agent respectively. The first part of the reducing agent is in the range of 30% to 40% of the total amount of the reducing agent.
Furthermore, the remaining amount of the alkali, the remaining amount of the alkylating agent and the remaining amount of the reducing agent are added to the mixture of compound of Formula II and the first fluid medium in parts.
In an exemplary embodiment of the present disclosure, the first part of the alkali is 40% of the total amount of the alkali, and the first part of the alkylating agent is 35% of the total amount of the alkylating agent.
The second part of the alkali is 7% of the total amount of the alkali, the second part of the alkylating agent is 13% of the total amount of the alkylating agent, and the first part of the reducing agent is 33% of the total amount of the reducing agent.
The remaining amount of the alkali is added in 7 equivalent parts, the remaining amount of the alkylating agent is added in 4 equivalent parts, and the remaining amount of the reducing agent is added in 2 equivalent parts.
Charging of the alkali, the alkylating agent, the reducing agent and the phase transfer catalyst in parts, facilitates in controlling the temperature of the reaction. It is observed that, maintaining the temperature of the reaction mixture within the range of 30°C to 60°C results in higher yield of the compound of Formula III along with high purity. Further, the compound of Formula II provides two sites for alkylation, i.e. ‘S’ and ‘N’. The addition of the alkali, the alkylating agent and the reducing agent in parts to the mixture of compound of Formula II and the first fluid medium allows the selective S-alkylation in presence of the unprotected primary amine functionality, and helps in reducing the amount of impurities arising out of N-alkylation.
In accordance with the embodiments of the present disclosure, the first fluid medium is water.
In accordance with the embodiments of the present disclosure, the alkali is selected from the group consisting of sodium hydroxide (NaOH), potassium hydroxide (KOH), sodium carbonate (Na2CO3), and potassium carbonate (K2CO3). In an exemplary embodiment of the present disclosure, the alkali is NaOH, and NaOH used is in the form of a 49% aqueous solution.
In accordance with the embodiments of the present disclosure, the mole ratio of 4-thiocyano-2-nitroaniline and the alkali is in the range of 1:4 to 1:8. In an exemplary embodiment of the present disclosure, the mole ratio of 4-thiocyano-2-nitroaniline and the alkali is 1:4.74.
In accordance with the embodiments of the present disclosure, the alkylating agent is selected from the group consisting of di-ethyl sulfate, and ethyl bromide (EtBr).
In an exemplary embodiment of the present disclosure, the alkylating agent is di-ethyl sulfate.
In accordance with the embodiments of the present disclosure, the mole ratio of 4-thiocyano-2-nitroaniline and the alkylating agent is in the range of 1:1 to 1:5. In an exemplary embodiment of the present disclosure, the mole ratio of 4-thiocyano-2-nitroaniline and the alkylating agent is 1:2.
In accordance with the embodiments of the present disclosure, the phase transfer catalyst is selected from the group consisting of tetra-n-butylammonium bromide, methyltrioctylammonium chloride, hexadecyltributylphosphonium bromide, and crown ethers. In an exemplary embodiment of the present disclosure, the phase transfer catalyst is tetra-n-butylammonium bromide.
In accordance with the embodiments of the present disclosure, the mole ratio of the 4-thiocyano-2-nitroaniline and the phase transfer catalyst is in the range of 1:0.005 to 1:0.05. In an exemplary embodiment of the present disclosure, the mole ratio of 4-thiocyano-2-nitroaniline and the phase transfer catalyst is 1:0.016.
In accordance with the embodiments of the present disclosure, the reducing agent is sodium hydrosulphide (NaSH), and sodium hydrosulfide is used in the form of 30% aqueous solution. Other reducing agents can also be used in the process of the present disclosure.
In accordance with the embodiments of the present disclosure, the mole ratio of 4-thiocyano-2-nitroaniline and the reducing agent is in the range of 1:0.5 to 1:1.0. In an exemplary embodiment of the present disclosure, the mole ratio of 4-thiocyano-2-nitroaniline and the reducing agent is 0.69.
In accordance with the embodiments of the present disclosure, the second fluid medium is selected from the group of fluids consisting of chlorobenzene, benzene, and toluene.
In accordance with the embodiments of the present disclosure, the third fluid medium is selected from a group of fluids consisting of chlorobenzene, toluene, benzene, DCM, and ethyl acetate, or a mixture of one or more of the fluids.
In an exemplary embodiment of the present disclosure, the second fluid medium and the third fluid both are monochlorobenzene.
In accordance with the embodiments of the present disclosure, the acid is acetic acid.
In accordance with the embodiments of the present disclosure, the mole ratio of 4-thiocyano-2-nitroaniline and the acid is in the range of 1:1 to 1:3. In an exemplary embodiment of the present disclosure, the mole ratio of 4-thiocyano-2-nitroaniline and the acid is 1:2.
In accordance with the embodiments of the present disclosure, the oxidizing agent is selected from the group consisting of hydrogen peroxide (H2O2), and m-chloro perbenzoic acid (m-CPBA). In an exemplary embodiment of the present disclosure, the oxidizing agent is hydrogen peroxide (H2O2), and H2O2 is used in the form of a 35% aqueous solution.
In accordance with the embodiments of the present disclosure, the mole ratio of 4-thiocyano-2-nitroaniline and the oxidizing agent is in the range of 1:2 to 1:3. In an exemplary embodiment of the present disclosure, the mole ratio of 4-thiocyano-2-nitroaniline and the oxidizing agent is 1:2.26.
In accordance with the embodiments of the present disclosure, the metal catalyst is sodium tungstate.
In accordance with the embodiments of the present disclosure, the mole ratio of 4-thiocyano-2-nitroaniline and the metal catalyst is in the range of 1:0.005 to 1:0.05. In an exemplary embodiment of the present disclosure, the mole ratio of 4-thiocyano-2-nitroaniline and the metal catalyst is 1:0.014.
In accordance with the embodiments of the present disclosure, the acid and the metal catalyst are used along with the oxidizing agent for oxidation of III. The use of the acid and the metal catalyst facilitates the selective S-oxidation in the presence of the unprotected primary amine functionality.
The process of the present disclosure is simple. Further, the process employs cheap and readily available reagents. Thus, the process of the present application is economical. Furthermore, the process of the present disclosure does not employ any protecting group for the amine functionality. Therefore the process of the present disclosure does not involve protection-deprotection sequence.
The present disclosure is further described in light of the following laboratory experiments which are set forth for illustration purpose only and not to be construed for limiting the scope of the disclosure. The following laboratory scale examples can be scaled up to industrial/commercial scale.
EXPERIMENTS
Experiment-I: Preparation of 4-ethanesulfonyl-2-nitroaniline (I)
A reactor was charged with water (1061 mL) and 4-thiocyano-2-nitroaniline (241.4 g, 1.23 moles) under continuous stirring at 25°C, to which NaOH (2.42 moles, 198 g of 49% aqueous solution) was added followed by addition of di-ethyl sulphate (134 g, 0.86 moles) and terta-butyl ammonium bromide (TBAB) (6.5 g, 0.02 moles). Stirring at 25°C was continued for another 15 min. Further, sodium hydroxide (NaOH) (3.4 moles, 277.5 g of 49% aqueous solution) was added in 8 equal parts followed by di-ethyl sulfate (248.5 g, 1.6 moles) in 5 equal parts and sodium hydrosulphide (NaSH) (0.852 moles, 159 g of 30% solution) in 3 equal parts to obtain a first reaction mixture. The progress of reaction was monitored by thin layer chromatography (TLC). After 4-thiocyano-2-nitroaniline was completely consumed (2 hours), stirring was stopped and the first reaction mixture was allowed to stand for 15 min to obtain a bi-phasic mixture comprising an aqueous layer and an organic layer. The organic layer and the aqueous layer were separated from the bi-phasic mixture. The aqueous layer so obtained was extracted with monochlorobenzene. The monochlorobenzene extract and the organic layer were mixed together to obtain a second mixture comprising 2-nitro-4-(ethylthio)aniline.
To the second reaction mixture, was added acetic acid (150 g, 2.5 moles) followed by sodium tungstate (5.06 g, 0.01 moles) and then heated at 55°C to obtain third reaction mixture. After 15 min, H2O2 (2.78 moles, 270 g of 35% aqueous solution) was added to the third reaction mixture over a time period of 3.5 hours while maintaining the temperature at 70°C and further stirred for 2 hours to obtain a product mixture. After completion of the reaction, the product mixture was cooled to 25°C, and water was added to obtain a suspension comprising a solid fraction comprising 4-ethanesulfonyl-2-nitroaniline and a liquid fraction. The solid fraction was filtered to obtain a residue. The residue was then washed with monochlorobenzene to obtain 245 g of 4-ethanesulfonyl-2-nitroaniline.
The purity of 4-ethanesulfonyl-2-nitroaniline was analyzed by HPLC, and was found to be 99%.
Melting point of 4-ethanesulfonyl-2-nitroaniline was 144°C -145°C.
Experiment-II: Preparation of 4-ethanesulfonyl-2-nitroaniline (I)
A reactor was charged with water (1061 mL) and 4-thiocyano-2-nitroaniline (241.4 g, 1.23 moles) under continuous stirring at 25°C, to which NaOH (2.42 moles, 198 g of 49% aqueous solution) was added followed by addition of di-ethyl sulphate (134 g, 0.86 moles) and terta-butyl ammonium bromide (TBAB) (6.5 g, 0.02 moles). Stirring at 25°C was continued for another 15 min. Further, sodium hydroxide (NaOH) (3.4 moles, 277.5 g of 49% aqueous solution) was added in 8 equal parts followed by di-ethyl sulfate (248.5 g, 1.6 moles) in 5 equal parts and sodium hydrosulphide (NaSH) (0.852 moles, 159 g of 30% solution) in 3 equal parts to obtain a first reaction mixture. The progress of reaction was monitored by thin layer chromatography (TLC). After 4-thiocyano-2-nitroaniline was completely consumed (2 hours), stirring was stopped and the first reaction mixture was allowed to stand for 15 min to obtain a bi-phasic mixture comprising an aqueous layer and an organic layer. The organic layer and the aqueous layer were separated from the bi-phasic mixture. The aqueous layer so obtained was extracted with monochlorobenzene. The monochlorobenzene extract and the organic layer were mixed together to obtain a second mixture comprising 2-nitro-4-(ethylthio)aniline.
To the second reaction mixture, was added acetic acid (115 g, 1.92 moles) followed by sodium tungstate (5.06 g, 0.01 moles) and then heated at 55°C to obtain third reaction mixture. After 15 min, H2O2 (2.78 moles, 270 g of 35% aqueous solution) was added to the third reaction mixture over a time period of 3.5 hours while maintaining the temperature at 70°C and further stirred for 2 hours to obtain a product mixture. After completion of the reaction, the product mixture was cooled to 25°C, and water was added to obtain a suspension comprising a solid fraction comprising 4-ethanesulfonyl-2-nitroaniline and a liquid fraction. The solid fraction was filtered to obtain a residue. The residue was then washed with monochlorobenzene to obtain 218 g of 4-ethanesulfonyl-2-nitroaniline.
It was observed from Experiment I and II that, yield of I decreased after the ratio of 4-thiocyno-2-nitroaniline and the acid (AcOH) was reduced to 1:1.5 from 1:2. The TLC analysis showed that 2-nitro-4-(ethylthio)aniline was not completely consumed during the oxidation step in the experiment II. Thus, the use of lower amount of the acid leads to incomplete oxidation of 2-nitro-4-(ethylthio)aniline.
Experiment-III: Preparation of 4-ethanesulfonyl-2-nitroaniline (I)
A reactor was charged with water (1061 mL) and 4-thiocyano-2-nitroaniline (241.4 g, 1.23 moles) under continuous stirring at 25°C, to which NaOH (2.42 moles, 198 g of 49% aqueous solution) was added followed by addition of di-ethyl sulphate (134 g, 0.86 moles) and terta-butyl ammonium bromide (TBAB) (6.5 g, 0.02 moles). Stirring at 25°C was continued for another 15 min. Further, sodium hydroxide (NaOH) (3.4 moles, 277.5 g of 49% aqueous solution) was added in 8 equal parts followed by di-ethyl sulfate (248.5 g, 1.6 moles) in 5 equal parts and sodium hydrosulphide (NaSH) (0.852 moles, 159 g of 30% solution) in 3 equal parts to obtain a first reaction mixture. The progress of the reaction was monitored by thin layer chromatography (TLC). After 4-thiocyano-2-nitroaniline was completely consumed (2 hours), stirring was stopped and the first reaction mixture was allowed to stand for 15 min to obtain a bi-phasic mixture comprising an aqueous layer and an organic layer. The organic layer and the aqueous layer were separated from the bi-phasic mixture. The aqueous layer so obtained was extracted with monochlorobenzene. The monochlorobenzene extract and the organic layer were mixed together to obtain a second mixture comprising 2-nitro-4-(ethylthio)aniline.
To the second reaction mixture, was added sulfuric acid (50%) (619 gm, 3.16 moles) followed by sodium tungstate (5.06 g, 0.01 moles) and then heated at 55°C to obtain third reaction mixture. After 15 min, H2O2 (4.46 moles, 433 g of 35% aqueous solution) was added to the third reaction mixture over a time period of 3.5 hours while maintaining the temperature at 70°C and further stirring for 2 hours to obtain a product mixture. TLC showed unreacted starting material.
It was observed from Experiment I and III that, use of 50% solution of sulphuric acid in place of acetic acid does not lead to desired product formation.

TECHNICAL ADVANCEMENTS
The present disclosure described herein above has several technical advantages including, but not limited to, the realization of a process for the preparation of 4-ethanesulfonyl-2-nitroaniline, that is:
- simple; and
- economical.
Throughout this specification the word “comprise”, or variations such as “comprises” or “comprising”, will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps.
The use of the expression “at least” or “at least one” suggests the use of one or more elements or ingredients or quantities, as the use may be in the embodiment of the invention to achieve one or more of the desired objects or results. While certain embodiments of the inventions have been described, these embodiments have been presented by way of example only, and are not intended to limit the scope of the inventions. Variations or modifications to the formulation of this invention, within the scope of the invention, may occur to those skilled in the art upon reviewing the disclosure herein. Such variations or modifications are well within the spirit of this invention.
The numerical values given for various physical parameters, dimensions and quantities are only approximate values and it is envisaged that the values higher than the numerical value assigned to the physical parameters, dimensions and quantities fall within the scope of the invention unless there is a statement in the specification to the contrary.
While considerable emphasis has been placed herein on the specific features of the preferred embodiment, it will be appreciated that many additional features can be added and that many changes can be made in the preferred embodiment without departing from the principles of the disclosure. These and other changes in the preferred embodiment of the disclosure will be apparent to those skilled in the art from the disclosure herein, whereby it is to be distinctly understood that the foregoing descriptive matter is to be interpreted merely as illustrative of the disclosure and not as a limitation. ,CLAIMS:1. A process for preparing 4-ethanesulfonyl-2-nitroaniline from 4-thiocyano-2-nitroaniline, said process comprising:
A. alkylating 4-thiocyano-2-nitroaniline with an alkylating agent in the presence of at least one alkali, at least one reducing agent, at least one phase transfer catalyst, and at least one first fluid medium to obtain 2-nitro-4-(ethylthio)aniline; and
B. oxidizing 2-nitro-4-(ethylthio)aniline with an oxidizing agent in the presence of at least one metal catalyst, and at least one acid to obtain 4-ethanesulfonyl-2-nitroaniline.
2. The process as claimed in claim 1, wherein in the step of alkylation, said alkali, said alkylating agent, said reducing agent, and said phase transfer catalyst are added to a mixture of 4-thiocyano-2-nitroaniline and said first fluid medium in one or more parts while maintaining the temperature of resultant mixture in the range of 20°C to 60°C.
3. The process as claimed in claim 1, wherein:
A. said process step of alkylating 4-thiocyano-2-nitroaniline comprises following sub-steps:
i. charging a reactor with 4-thiocyano-2-nitroaniline and said first fluid medium to obtain a mixture;
ii. adding said alkali, said alkylating agent, said reducing agent, and said phase transfer catalyst to the mixture in one or more parts while maintaining the temperature of the mixture in the range of 20°C to 60°C, to obtain a first reaction mixture;
iii. stirring said first reaction mixture at a temperature in the range 20°C to 60°C for a time period in the range of 1 hour to 10 hours, and stopping the stirring to obtain a bi-phasic mixture comprising an aqueous phase and an organic phase containing 2-nitro-4-(ethylthio)aniline;
iv. separating said organic phase and said aqueous phase from said bi-phasic mixture, followed by extracting separated aqueous phase with at least one second fluid medium and mixing said extract/s with separated organic phase to obtain a second reaction mixture comprising 2-nitro-4-(ethylthio)aniline;
B. said process step of oxidizing 2-nitro-4-(ethylthio)aniline comprises following sub-steps:
v. adding said acid and said metal catalyst to said second reaction mixture and stirring at a temperature in the range 30°C to 100°C for a time period in the range of 1 hour to 10 hours, followed by adding said oxidizing agent over a time period in the range of 2 hours to 5 hours while maintaining the temperature in the range of 30°C to 100°C for a time period in the range of 1 hour to 10 hours to obtain a product mixture;
vi. cooling said product mixture to a temperature in the range of 10°C to 25°C and adding water to obtain a suspension comprising a solid fraction containing 4-ethanesulfonyl-2-nitroaniline and a liquid fraction, followed by separating said solid fraction containing 4-ethanesulfonyl-2-nitroaniline from said suspension to obtain a residue; and
vii. washing said residue with a third fluid medium and drying to obtain 4-ethanesulfonyl-2-nitroaniline having a purity in the range of 98% to 99.9%.
4. The process as claimed in claim 3, wherein in step (ii)
• said phase transfer catalyst is added in one part;
• said alkali is added in 4 to 10 parts, and amount of each part of the alkali is in the range of 5% to 50% of the total amount of the alkali;
• said alkylating agent is added in 2 to 8 parts, and amount of each part of the alkylating agent is in the range of 10% to 50% of the total amount of the alkylating agent; and
• said reducing agent is added in 2 to 6 parts, and amount of each part of the reducing agent is 15% to 75% of the total amount of the reducing agent.
5. The process as claimed in any one of claim 1, claim 2, and claim 3, wherein said alkali is selected from the group consisting of sodium hydroxide, potassium hydroxide, sodium carbonate, and potassium carbonate, and the mole ratio of 4-thiocyano-2-nitroaniline and said alkali is in the range of 1:4 to 1:8.
6. The process as claimed in any one of claim 1, claim 2, and claim 3, wherein said alkylating agent is selected from the group consisting of di-ethyl sulfate and ethyl bromide, and the mole ratio of 4-thiocyano-2-nitroaniline and said alkylating agent is in the range of 1:1 to 1:5.
7. The process as claimed in any one of claim 1, claim 2, and claim 3, wherein said reducing agent is sodium hydrosulfide, and the mole ratio of 4-thiocyano-2-nitroaniline and said reducing agent is in the range of 1:0.5 to 1:1.0.
8. The process as claimed in any one of claim 1, claim 2, and claim 3, wherein said phase transfer catalyst is selected from the group consisting of tetra-n-butylammonium bromide, methyltrioctylammonium chloride, hexadecyltributylphosphonium bromide, and crown ethers, and the mole ratio of 4-thiocyano-2-nitroaniline and said phase transfer catalyst is in the range of 1:0.005 to 1:0.05.
9. The process as clamed in any one of claim 1, claim 2, and claim 3, wherein said oxidizing agent is selected from the group consisting of hydrogen peroxide , and m-chloroperbenzoic acid, and the mole ratio of 4-thiocyano-2-nitroaniline and said oxidizing agent is in the range of 1:2 to 1:3.
10. The process as claimed in claim any one of claim 1, claim 2, and claim 3, wherein said metal catalyst is sodium tungstate, and the mole ratio of 4-thiocyano-2-nitroaniline and said metal catalyst is in the range of 1:0.005 to 1:0.05.
11. The process as claimed in any one of claim 1, claim 2, and claim 3, wherein said acid is acetic acid, and the mole ratio of 4-thiocyano-2-nitroaniline and said acid is in the range of 1:1 to 1:3.
12. The process as claimed in any one of claim 1, claim 2, and claim 3, wherein said first fluid medium is water.
13. The process as claimed in claim 3, wherein said second fluid medium is at least one selected from the group of fluids consisting of chlorobenzene, benzene, and toluene and third fluid medium is at least one selected from a group of fluids consisting of chlorobenzene, toluene, benzene, dichloromethane, and ethyl acetate.